The current generation of continuous glucose monitors (CGMs) are designed to be implanted transdermally for up to seven days after which the transducer is replaced by the wearer. Despite current advances in the analytical merits of these devices, CGMs are still limited to the quantification of a single analyte (glucose) over relatively short periods of time. However, it is increasingly recognized that proper glycemic management requires a more comprehensive examination of metabolic function. Blood catecholamines and ketones are some examples of neurotransmitters and metabolites that can augment standard blood glucose measurements, hence providing added dimensions of information pertaining to the patient's glycemic control and overall metabolic health. Moreover, a reduction in the frequency that the transducer element is replaced would further simplify the operation of CGMs and provide increased autonomy in the patient's routine. In light of the current limitations of CGMs, our team has recently pioneered the development of a minimally-invasive body-worn patch containing an addressable microneedle array with multiplexed sensing elements. Owing to the novel method in which the electrochemical transducer is embedded within the apertures of an array of hollow microneedles, the on-body biosensor is able to perform various bioanalytical functions directly at the microneedle-transdermal fluid interface and does not require sophisticated microelectromechanical or microfluidic systems for fluid extraction and analysis. The novel implementation of conducting polymers provides for both an effective means for the entrapment of the biorecognition element as well as the ability to impart a high degree of perm-selectivity, thereby dramatically extending the biosensor's useful lifetime and specificity. Furthermore, the utilization of a fluorocarbon paste mitigates the oxygen dependency that obfuscates accurate blood glucose readings among current CGM solutions. In accordance with the project plan, the research effort seeks to attain the following objectives: (1) design and fabrication of the multi-analyte microneedle array sensor platform, (2) surface immobilization and surface chemistry, and (3) critical evaluation of the system performance. The proposed Phase I research aims at extending the microneedle array concept up to the stage of preliminary clinical studies in order transform this laboratory-proven technology into a commercial product that can serve as a major contender in the USD $17B global market for glucose monitoring devices and artificial pancreas systems. The technology and business objectives outlined in this proposal will have a direct impact on basic research and clinical applications to enhance the current state of glycemic management and thereby will improve the well-being of the population with diabetes.